We are proposing a fundamentally new approach for the treatment of malignant brain tumors. The discovery and development, by members of this NCDDC, of biodegradable and biocompatible controlled release polymers has enabled us to bypass the limitations of the blood-brain barrier and expose the growing brain tumor to high drug concentrations for extended intervals. This approach can effectively administer chemotherapeutic agents as well as rationally designed new drugs and biological agents. The local, prolonged release of drugs at the site of tumor growth exposes the tumor to high levels of the drug while minimizing systemic exposure and toxicity and therefore health care costs. Program l, headed by Dr Henry Brem, will investigate the effectiveness and safety of new formulations of controlled-release drug delivery for the treatment of brain tumors. Program 2, headed by Dr. Robert Langer, will provide new polymer formulations. Program 3, headed by Dr. W. Mark Saltzman, will construct mathematical models for predicting drug distribution and clearance in the brain. Program 4, headed by Dr. O. Michael Colvin, will develop chemotherapy agents which are appropriate for incorporation into polymers for local therapy and design new agents. Program 5, headed by Dr. Drew Pardoll, will investigate polymer delivery of cytokines to develop brain tumor vaccines. Core B, headed by Dr. Craig Smith, will provide polymers that are prepared with new methods and develop the scale up and purification of the polymers. The programs of this NCDDG have been working together as a cohesive, collaborative group. Our productivity is reflected in a number of new discoveries by this group which hassled to over 150 publications during the past four years, most of which involve interactions between the different programs. This cooperative effort has allowed us to design and carry out a series of pre-clinical studies to evaluate this new, potentially curative, cancer treatment. Our effort has led to the initiation of five multi-institutional, FDA-approved clinical trials of BCNU impregnated polymers. The NCI is funding a separate UO1 for a Hopkins Clinical Consortium to support Phase 1 testing of the polymers developed in this NCDDG. We are hopeful that with the continued support and participation of the NCI we can continue to interact synergistically and develop fully the promise of this new approach.